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Intraoperative OCT (iOCT) is an innovative imaging modality that provides ophthalmic surgeons with real-time cross-sectional views of the surgical field. Recent advances in OCT technology, such as higher acquisition scanning rates, enable real-time video visualization. iOCT systems are widely used in both vitreoretinal and anterior segment surgeries. In corneal surgeries, iOCT imaging aims to optimize efficacy and safety by improving depth perception and enhancing visualization in cases of opaque optical media. iOCT is a valuable tool not only for experienced corneal surgeons, but also for training novice surgeons. This review summarizes the emerging applications of iOCT in corneal surgery, particularly in technically demanding lamellar keratoplasty procedures, as well as in various other corneal diseases and complications that require surgical intervention. [ABSTRACT FROM AUTHOR]

Creatine kinases are essential for maintaining cellular energy balance by facilitating the reversible transfer of a phosphoryl group from ATP to creatine, however, their role in mitochondrial ATP production remains unknown. This study shows creatine kinases, including CKMT1A, CKMT1B, and CKB, are highly expressed in cells relying on the mitochondrial F1F0 ATP synthase for survival. Interestingly, silencing CKB, but not CKMT1A or CKMT1B, leads to a loss of sensitivity to the inhibition of F1F0 ATP synthase in these cells. Mechanistically, CKB promotes mitochondrial ATP but reduces glycolytic ATP production by suppressing mitochondrial calcium (mCa2+) levels, thereby preventing the activation of mitochondrial permeability transition pore (mPTP) and ensuring efficient mitochondrial ATP generation. Further, CKB achieves this regulation by suppressing mCa2+ levels through the inhibition of AKT activity. Notably, the CKB‐AKT signaling axis boosts mitochondrial ATP production in cancer cells growing in a mouse tumor model. Moreover, this study also uncovers a decline in CKB expression in peripheral blood mononuclear cells with aging, accompanied by an increase in AKT signaling in these cells. These findings thus shed light on a novel signaling pathway involving CKB that directly regulates mitochondrial ATP production, potentially playing a role in both pathological and physiological conditions. [ABSTRACT FROM AUTHOR]

The synthesis of optically active compounds requires determination of ee, er, and enantiomeric purity. The aim of the present paper is to review the synthesis of several chiral derivatizing reagents (CDRs) in a rational manner, which were successful for the separation and isolation of enantiomers of a variety of active pharmaceutical ingredients and other important and useful racemates. Besides, the application of (i) certain enantiomerically pure amines, either directly or by incorporating each of them as chiral auxiliary in difluorodinitrobenzene or cyanuric chloride moieties to construct the CDR, (ii) (S)-ketoprofen and (S)-levofloxacin as chiral platforms, and (iii) a few isothiocyanates, have been suitably included. Attention is drawn to the use of water micellar mobile phase as the "green" RP-HPLC method and the use of simple achiral derivatization with ninhydrin, particularly. Synthesis of CDRs and their application for enantioseparation of racemates and detagging of certain chromophoric reagent components for obtaining native enantiomers are other interesting features included herein. The methods can be easily used to determine and control enantiomeric purity with advantages over a variety of commercial chiral phases. This comprehensive review not only highlights innovative methodologies for enantioseparation but also underscores their practical applications in controlling and ensuring the enantiomeric purity of pharmaceutical compounds., (© 2024 John Wiley & Sons Ltd.)

Enantiomers of a chiral active pharmaceutical ingredient (API) often exhibit different physicochemical, pharmacokinetic, and biological properties. Therefore, enantioseparation becomes a critical aspect of pharmaceutical development. Sertraline, one of the most widely prescribed antidepressant medications, requires purification from its chiral impurities, and this is recommended and essential for its quality control. This perspective highlights the current established research on the separation and quantification of sertraline's chiral impurities, with a focus on instrumental and crystallization-based techniques., (© 2024 John Wiley & Sons Ltd.)

The Ras–mitogen-activated protein kinase (MAPK) pathway is a major target for cancer treatment. To better understand the genetic pathways that modulate cancer cell sensitivity to MAPK pathway inhibitors, we performed a CRISPR knockout screen with MAPK pathway inhibitors on a colorectal cancer (CRC) cell line carrying mutant KRAS. Genetic deletion of the catalytic subunit of protein phosphatase 6 (PP6), encoded by PPP6C, rendered KRAS- and BRAF-mutant CRC and BRAF-mutant melanoma cells more resistant to these inhibitors. In the absence of MAPK pathway inhibition, PPP6C deletion in CRC cells decreased cell proliferation in two-dimensional (2D) adherent cultures but accelerated the growth of tumor spheroids in 3D culture and tumor xenografts in vivo. PPP6C deletion enhanced the activation of nuclear factor κB (NF-κB) signaling in CRC and melanoma cells and circumvented the cell cycle arrest and decreased cyclin D1 abundance induced by MAPK pathway blockade in CRC cells. Inhibiting NF-κB activity by genetic and pharmacological means restored the sensitivity of PPP6C-deficient cells to MAPK pathway inhibition in CRC and melanoma cells in vitro and in CRC cells in vivo. Furthermore, a R264 point mutation in PPP6C conferred loss of function in CRC cells, phenocopying the enhanced NF-κB activation and resistance to MAPK pathway inhibition observed for PPP6C deletion. These findings demonstrate that PP6 constrains the growth of KRAS- and BRAF-mutant cancer cells, implicates the PP6–NF-κB axis as a modulator of MAPK pathway output, and presents a rationale for cotargeting the NF-κB pathway in PPP6C-mutant cancer cells. Editor's summary: Inhibitors of the Ras-MAPK pathway are used to treat cancers carrying RAS and BRAF mutations. Zhang et al. performed a CRISPR-based screen to find modulators of the MAPK pathway and found that protein phosphatase 6 (PP6) increased sensitivity to MAPK pathway inhibitors. Deletion of the catalytic subunit of PP6 promoted the growth of KRAS- and BRAF-mutant cells in spheroid cultures and in mice in an NF-κB–dependent manner and increased their resistance to MAPK pathway inhibitors. These findings indicate that PP6 contributes to MAPK sensitivity in KRAS- and BRAF-mutant cells and suggest that the NF-κB pathway may be cotargeted in PP6C-mutant cells. —Amy E. Baek [ABSTRACT FROM AUTHOR]

Ni anisotropic microgroove structures were prepared by lithographic processes and electroforming to investigate the effect of microstructures on friction forces. For Ni microgroove structures, the friction forces varied significantly depending on the indenter sliding direction to the anisotropic microstructures. The friction forces of parallel sliding directions on microgroove structures were unstable and considerably larger than those of the perpendicular directions owing to the difference in the structure continuousness. These results suggest that anisotropic microstructures affect friction forces and can deploy fail-safe functions when a large load is accidentally applied. [ABSTRACT FROM AUTHOR]

This article explores the use of organic photocatalysts (OPCs) in photoredox catalysis, a method for achieving molecular transformations under mild conditions. The authors focus on developing highly reducing OPCs as an alternative to expensive noble-metal-based catalysts. They specifically study small aromatics with two diarylamino termini as OPCs, which have shown promising redox abilities. The article also discusses the applications of these OPCs in regioselective radical fluoroalkylation reactions, which are useful for synthesizing fluorine-containing compounds. The authors investigate different photocatalysts and fluoroalkylating reagents to induce these reactions, highlighting the potential of these sustainable organic synthesis methods. [Extracted from the article]

We report a case of a man in his 70s who developed haemoptysis 3 days after commencing sildenafil. Before postulating a potential connection between sildenafil use and haemoptysis, it is important to rule out potential other causative factors and comorbidities. The patient suffers from multiple medical conditions and takes various medications. On examination, no abnormalities were discovered. There were no recent significant changes in his bloodwork. Cessation of sildenafil coincided with spontaneous symptom resolution. Chest CT was performed, and no abnormalities were reported. Pseudohaemoptysis or malignancy may be the main differential diagnoses of haemoptysis in elderly patients with multiple comorbidities. Concurrent anticoagulation of the patient may predispose to haemoptysis and is likely to be of greater clinical concern. [ABSTRACT FROM AUTHOR]

Herein the development of cellular impedance biosensors, electrochemical impedance spectroscopy, and the general principles and terms associated with the cell–electrode interface is reviewed. This family of techniques provides quantitative and sensitive information into cell responses to stimuli in real-time with high temporal resolution. The applications of cell-based impedance biosensors as a readout in cell biology is illustrated with a diverse range of examples. The current state of the field, its limitations, the possible available solutions, and the potential benefits of developing biosensors are discussed. [ABSTRACT FROM AUTHOR]

Sleep apnea syndrome (SAS) exposes cells throughout the body to intermittent hypoxia (IH). Intermittent hypoxia is a risk factor not only for hypertension and insulin resistance but also for vascular dysfunction. We have reported correlations between IH, insulin resistance and hypertension. However, the details of why IH leads to vascular dysfunction remain unclear. In this study, we investigated inflammation‐related transcripts in vascular endothelial cells (human HUEhT‐1 and mouse UV2) exposed to IH by real‐time RT‐PCR and found that intercellular adhesion molecule‐1 (ICAM‐1) and endothelial cell‐specific molecule‐1 (ESM1) mRNAs were significantly increased. ELISA confirmed that, in the UV2 cell medium, ICAM‐1 and ESM1 were significantly increased by IH. However, the promoter activities of ICAM‐1 and ESM1 were not upregulated. On the other hand, IH treatment significantly decreased microRNA (miR)‐181a1 in IH‐treated cells. The introduction of miR‐181a1 mimic but not miR‐181a1 mimic NC abolished the IH‐induced upregulation of Ican‐1 and ESM1. These results indicated that ICAM‐1 and ESM1 were upregulated by IH via the IH‐induced downregulation of miR‐181a1 in vascular endothelial cells and suggested that SAS patients developed atherosclerosis via the IH‐induced upregulation of ICAM‐1 and ESM1. [ABSTRACT FROM AUTHOR]

Graphitic carbon nitride is widely studied in organic photoredox catalysis. Reductive quenching of carbon nitride excited state is postulated in many photocatalytic transformations. However, the reactivity of this species in the turn over step is less explored. In this work, we investigate electron and proton transfer from carbon nitride that is photocharged to a various extent, while the negative charge is compensated either by protons or ammonium cations. Strong stabilization of electrons by ammonium cations makes proton-coupled electron transfer uphill, and affords air-stable persistent carbon nitride radicals. In carbon nitrides, which are photocharged to a smaller extent, protons do not stabilize electrons, which results in spontaneous charge transfer to oxidants. Facile proton-coupled electron transfer is a key step in the photocatalytic oxidative-reductive cascade – tetramerization of benzylic amines. The feasibility of proton-coupled electron transfer is modulated by adjusting the extent of carbon nitride photocharging, type of counterion and temperature.Savateev et al. investigate proton-coupled electron transfer from persistent graphitic carbon nitride radical to oxygen and imines. The results of their study find application in cascade photocatalysis – selective tetramerization of benzylic amines. [ABSTRACT FROM AUTHOR]

Sonoporation refers to the formation of tiny transient pores in cell plasma membranes by using ultrasound to increase the permeability to bioactive materials. Recently, the Sonoporation technique has been widely researched in cell treatment applications, such as gene transfection. However, due to the random distribution of microbubbles, it is challenging to perform controllable and precise localized sonoporation of a target cell. In this work, a device based on the surface acoustic wave is developed to achieve a selective manipulation and cavitation of microbubbles. The device consists of a pair of microbubble positioning slant‐finger interdigital transducers (SFITs) for moving a selected microbubble in a two‐dimensional plane. Meanwhile, another narrow‐frequency‐band SFIT is integrated into the device for local cavitation control of the same microbubble. As a result, a microbubble can be transported orthogonal to and along the acoustic transmission path by continuously adjusting the input frequency and relative phase. Upon reaching the target cell, the selected microbubble can be cavitated without exciting other microbubbles, resulting in local sonoporation. The resolution of phase‐based positioning and frequency‐based transportation are 8.3 and 7.0 µm with 45° and 10 kHz settings, respectively. [ABSTRACT FROM AUTHOR]

In this study, a 3-stage power amplifier monolithic microwave integrated circuits (MMIC) in the Ku-band frequency range is designed using a 150-nanometer GaN-HEMT process. High efficiency is achieved by employing a high-pass structure at the output stage to reduce the circuit size and selecting a high output impedance at the driver amplification stage. When measuring the power amplifier using a 0.5 ms period and 10 % duty cycle pulse continuous wave (CW) signal, the results indicate a saturated power of 37∼38 dBm in the 13∼16 GHz range with a power added efficiency (PAE) of 34∼41 % and a power gain of 26∼30 dB. The power amplifier is sized 3.6×1.1 mm², demonstrating suitability for use in the transmission section of satellite communication modules. [ABSTRACT FROM AUTHOR]

Autoimmunity is reported involving in reproductive failures, and antinuclear antibody (ANA) positivity has been regarded as a typical feature of autoimmunity. Published studies on the association of ANA with reproductive failures including infertility are controversial. The aim of this meta‐analysis was to analyse whether the presence of ANA positivity increases the risk of infertility in women. We searched the PubMed and Embase databases for relevant literature without any restrictions prior to April 28, 2021. All analyses were performed using the RevMan 5.3 software. Twelve studies with 2734 participants, including 1482 patients with infertility, met the inclusion and exclusion criteria. The total positivity rate of ANA was 23.8% (353/1482) in all infertile patients and 8.5% (107/1252) in the control group. Infertile females had a significantly higher ANA positivity rate than the control group (odds ratio [OR] = 2.90, 95% confidence interval [CI]: 1.72–4.87, I2 = 65%, P <.0001). Several subgroup analyses were performed to reduce the heterogeneity. ANA positivity was associated with female infertility in studies either performed by indirect immunofluorescence (OR = 2.26, 95% CI:1.67–3.06, P <.00001) or by ELISA (OR = 10.76, 95% CI:1.82–63.64, P <.00001). ANA was significantly associated with increased risk of women infertility either after the definite exclusion of individuals with autoimmune diseases (AID) or without exclusion [(OR = 1.99, 95% CI:1.29–3.06, P =.002), (OR = 2.76, 95% CI:1.56–4.88, P =.0005), respectively]. This meta‐analysis provides a comprehensive overview of the prevalence of antinuclear antibodies (ANA) in infertile women and suggests that ANA positivity increases the risk of infertility. [ABSTRACT FROM AUTHOR]

The photoreduction of hexavalent chromium (Cr(VI)) using TiO2 adsorbed gold nanoparticles and perylene (Au/Pe/TiO2) as a novel organic–inorganic hybrid photocatalyst has been studied. The irradiation by a Xe lamp of a Cr (VI) aqueous solution (0.1 mM) with the Au/Pe/TiO2 powder resulted in the reduction of the Cr(VI). The rate of Cr(VI) reduction reached 98.3% by the irradiation for 60 min. The reaction rate constant using Au/Pe/TiO2 (0.0545 min−1) was higher than that of TiO2 (0.0218 min−1), Pe/TiO2 (0.0303 min−1), or Au/TiO2 (0.0393 min−1). Gold nanoparticles and perylene synergistically accelerated the TiO2 photocatalytic reaction. This result is due to the Z-scheme electron transfer between Pe and TiO2 and the suppression of charge recombination by the gold nanoparticles. The irradiation of sunlight also led to the photocatalytic reduction of the Cr(VI) by Au/Pe/TiO2. In addition, successive reduction of the Cr(VI) was achieved by using a column packed with the Au/Pe/TiO2 powder immobilized by calcium alginate gel. [ABSTRACT FROM AUTHOR]

Intraoperative OCT is an innovative and promising technology which allows anterior and posterior segment ocular surgeons to obtain a near-histologic cross-sectional and tomographic image of the tissues. Intraoperative OCT has several applications in ocular surgery which are particularly interesting in the context of corneal transplantation. Indeed, iOCT images provide a direct and meticulous visualization of the anatomy, which could guide surgical decisions. In particular, during both big-bubble and manual DALK, the visualization of the relationship between the corneal layers and instruments allows the surgeon to obtain a more desirable depth of the trephination, thus achieving more type 1 bubbles, better regularity of the plane, and a reduced risk of DM perforation. During EK procedures, iOCT supplies information about proper descemetorhexis, graft orientation, and interface quality in order to optimize the postoperative adhesion and reduce the need for re-bubbling. Finally, mushroom PK, a challenging technique for many surgeons, can be aided through the use of iOCT since it guides the correct apposition of the lamellae and their centration. The technology of iOCT is still evolving: a larger field of view could allow for the visualization of all surgical fields, and automated tracking and iOCT autofocusing guarantee the continued centration of the image. [ABSTRACT FROM AUTHOR]

Cemented polished tapered femoral stems (PTS) made of cobalt–chrome alloy (CoCr) are a known risk factor for periprosthetic fracture (PPF). The mechanical differences between CoCr-PTS and stainless-steel (SUS) PTS were investigated. CoCr stems having the same shape and surface roughness as the SUS Exeter® stem were manufactured and dynamic loading tests were performed on three each. Stem subsidence and the compressive force at the bone–cement interface were recorded. Tantalum balls were injected into the cement, and their movement was tracked to indicate cement movement. Stem motions in the cement were greater for the CoCr stems than for the SUS stems. In addition, although we found a significant positive correlation between stem subsidence and compressive force in all stems, CoCr stems generated a compressive force over three times higher than SUS stems at the bone–cement interface with the same stem subsidence (p < 0.01). The final stem subsidence amount and final force were greater in the CoCr group (p < 0.01), and the ratio of tantalum ball vertical distance to stem subsidence was significantly smaller for CoCr than for SUS (p < 0.01). CoCr stems appear to move more easily in cement than SUS stems, which might contribute to the increased occurrence of PPF with the use of CoCr-PTS. [ABSTRACT FROM AUTHOR]

In this paper, we have proposed a Multiservice Provisioning Optical Code Switching (OCS) method for GMPLS networks, which uses Optical-Code-Division-Multiplexing (OCDM) across every lightpath of a wavelength division multiplexing system. We also presented the router architecture for the GMPLS multiservice network. In this method, the Multi Length Variable Weight Optical Orthogonal Code (MLVW-OOC) is used to multiplex each class (two-class system) service connection to a wavelength as an OCDM signature series. First, the fiber bandwidth has been classified into several wavebands, whose wavelengths are considered for a specific service class depending on the characteristics of that service class. The codes corresponding to the service class are also given in this manuscript. Erlang's traffic behavior of the network model is used to evaluate the system performance as well as to obtain the probability density functions (PDF) of the number of labels oocupied by a link. We have also evaluated the PDF for the number of labels occupied in each wavelength. Further, we have evaluated the performance of the network in terms of the probability of outage, blocking probability, and the end-to-end (EE) bit error rate (BER) of a connection. The results indicate that interfering users perform better with longer-weight code words. Moreover, with the increase in the number of intermediate OCS routers, EE BER is increased, and it is found that by constraining the number of connected paths, performance can be improved. [ABSTRACT FROM AUTHOR]

Modern western dietary habits and low physical activity cause metabolic abnormalities and abnormally elevated levels of metabolites such as low-density lipoprotein, which can lead to immune cell activation, and inflammatory reactions, and atherosclerosis. Appropriate stimulation of vascular endothelial cells can confer protective responses against inflammatory reactions and atherosclerotic conditions. This study aims to determine whether a designed optogenetic approach is capable of affecting functional changes in vascular endothelial cells and to evaluate its potential for therapeutic regulation of vascular inflammatory responses in vitro. We employed a genetically engineered, blue light-activated Ca2+ channel switch molecule that utilizes an endogenous store-operated calcium entry system and induces intracellular Ca2+ influx through blue light irradiation and observed an increase in intracellular Ca2+ in vascular endothelial cells. Ca2+-dependent activation of the nuclear factor of activated T cells and nitric oxide production were also detected. Microarray analysis of Ca2+-induced changes in vascular endothelial cells explored several genes involved in cellular contractility and inflammatory responses. Indeed, there was an increase in the gene expression of molecules related to antiinflammatory and vasorelaxant effects. Thus, a combination of human blue lightactivated Ca2+ channel switch 2 (hBACCS2) and blue light possibly attenuates TNFa- induced inflammatory NF-B activity. We propose that extrinsic cellular Ca2+ regulation could be a novel approach against vascular inflammation. [ABSTRACT FROM AUTHOR]

Background: Running gait assessment has traditionally been performed using subjective observation or expensive laboratory-based objective technologies, such as three-dimensional motion capture or force plates. However, recent developments in wearable devices allow for continuous monitoring and analysis of running mechanics in any environment. Objective measurement of running gait is an important (clinical) tool for injury assessment and provides measures that can be used to enhance performance. Objectives: We aimed to systematically review the available literature investigating how wearable technology is being used for running gait analysis in adults. Methods: A systematic search of the literature was conducted in the following scientific databases: PubMed, Scopus, Web of Science and SPORTDiscus. Information was extracted from each included article regarding the type of study, participants, protocol, wearable device(s), main outcomes/measures, analysis and key findings. Results: A total of 131 articles were reviewed: 56 investigated the validity of wearable technology, 22 examined the reliability and 77 focused on applied use. Most studies used inertial measurement units (n = 62) [i.e. a combination of accelerometers, gyroscopes and magnetometers in a single unit] or solely accelerometers (n = 40), with one using gyroscopes alone and 31 using pressure sensors. On average, studies used one wearable device to examine running gait. Wearable locations were distributed among the shank, shoe and waist. The mean number of participants was 26 (± 27), with an average age of 28.3 (± 7.0) years. Most studies took place indoors (n = 93), using a treadmill (n = 62), with the main aims seeking to identify running gait outcomes or investigate the effects of injury, fatigue, intrinsic factors (e.g. age, sex, morphology) or footwear on running gait outcomes. Generally, wearables were found to be valid and reliable tools for assessing running gait compared to reference standards. Conclusions: This comprehensive review highlighted that most studies that have examined running gait using wearable sensors have done so with young adult recreational runners, using one inertial measurement unit sensor, with participants running on a treadmill and reporting outcomes of ground contact time, stride length, stride frequency and tibial acceleration. Future studies are required to obtain consensus regarding terminology, protocols for testing validity and the reliability of devices and suitability of gait outcomes. Clinical Trial Registration: CRD42021235527. [ABSTRACT FROM AUTHOR]

An improved mathematical model of soft heart tissue has been developed here. Nonlinear material equations were derived from the fundamental principles of nonequilibrium thermodynamics. The passive and active phases of cardiac tissue deformation are considered using the nonlinear theory of hyperelasticity. Elastic potentials for both phases are presented in a simple form convenient for numerical calculations. To take into account muscle contraction in the active phase of deformation, coupled equations of mechanochemical kinetics are obtained. The proposed model can be used for computer modeling of the heart and circulatory system. [ABSTRACT FROM AUTHOR]

A dysregulation of the cell-death mechanism contributes to poor prognosis in lung cancer. New potent chemotherapeutic agents targeting apoptosis-deregulating molecules have been discovered. In this study, 22-(4-pyridinecarbonyl) jorunnamycin A (22-(4′py)-JA), a synthetic derivative of bistetrahydroisoquinolinequinone from the Thai blue sponge, was semisynthesized by the Steglich esterification method, and its pharmacological mechanism in non-small-cell lung cancer (NSCLC) was elucidated by a network pharmacology approach. All predicted targets of 22-(4′py)-JA and genes related to NSCLC were retrieved from drug-target and gene databases. A total of 78 core targets were identified, and their associations were analyzed by STRING and Cytoscape. Gene ontology and KEGG pathway enrichment analyses revealed that molecules in mitogen-activated protein kinase (MAPK) signaling were potential targets of 22-(4′py)-JA in the induction of NSCLC apoptosis. In silico molecular docking analysis displayed a possible interaction of ERK1/2 and MEK1 with 22-(4′py)-JA. In vitro anticancer activity showed that 22-(4′py)-JA has strong cytotoxic and apoptosis-inducing effects in H460, H292 and A549 NSCLC cells. Furthermore, immunoblotting confirmed that 22-(4′py)-JA induced apoptotic cell death in an ERK/MEK/Bcl-2-dependent manner. The present study demonstrated that 22-(4′py)-JA exhibited a potent anticancer effect that could be further developed for clinical application and showed that network pharmacology approaches are a powerful tool to illustrate the molecular pathways of new drugs or compounds. [ABSTRACT FROM AUTHOR]

The pathogenesis of osteoporosis (OP) is closely associated with the disrupted balance between osteogenesis and adipogenesis in bone marrow-derived mesenchymal stem cells (BMSCs). We analyzed published single-cell RNA sequencing (scRNA-seq) data to dissect the transcriptomic profiles of bone marrow-derived cells in OP, reviewing 56 377 cells across eight scRNA-seq datasets from femoral heads (osteoporosis or osteopenia n = 5, osteoarthritis n = 3). Seventeen genes, including carboxypeptidase M (CPM), were identified as key osteogenesis-adipogenesis regulators through comprehensive gene set enrichment, differential expression, regulon activity, and pseudotime analyses. In vitro, CPM knockdown reduced osteogenesis and promoted adipogenesis in BMSCs, while adenovirus-mediated CPM overexpression had the reverse effects. In vivo, intraosseous injection of CPM-overexpressing BMSCs mitigated bone loss in ovariectomized mice. Integrated scRNA-seq and bulk RNA sequencing analyses provided insight into the MAPK/ERK pathway's role in the CPM-mediated regulation of BMSC osteogenesis and adipogenesis; specifically, CPM overexpression enhanced MAPK/ERK signaling and osteogenesis. In contrast, the ERK1/2 inhibitor binimetinib negated the effects of CPM overexpression. Overall, our findings identify CPM as a pivotal regulator of BMSC differentiation, which provides new clues for the mechanistic study of OP., (© 2024 Federation of American Societies for Experimental Biology.)

Studies evaluating pregnancy outcomes in systemic sclerosis (SSc) are limited. SSc is associated with maternal complications and adverse neonatal outcomes. This study investigated the impact of disease stage (stable vs active) on the maternal and neonatal outcomes of pregnancies of patients followed at an Israeli medical centre. The charts of 354 SSc female patients followed during 2003–2020 were reviewed. Data on clinical and laboratory features, number of pregnancies close to SSc diagnosis, and maternal and neonatal outcomes were analysed. Patients were divided into a stable disease and an active/early disease group. The active/early disease group included 26 patients [19 diffuse SSc (dSSc)], with 38 pregnancies. Median disease duration was 1 year, except for four patients who were first diagnosed during pregnancy. SSc was exacerbated in all patients during pregnancy or shortly after delivery [skin, lung, and heart involvement in dSSc; severe vasculopathy in limited SSc patients]. Six patients had hypertensive disorders of pregnancy; four pregnancies ended with foetal death. Thirty-three children were born, 60% with intrauterine growth retardation (IUGR)/low birthweight (LBW). The stable disease group included 19 patients, including seven with previously active disease, now stabilized (five dSSc), and 32 pregnancies. All pregnancies were planned and monitored closely. Disease remained stable in all patients. Four patients had hypertensive disorders of pregnancy; 12/29 newborns had LBW (41%). Active maternal disease during pregnancy poses an increased risk of SSc aggravation. The maternal and neonatal outcomes in planned pregnancy during stable disease are favourable. IUGR/LBW is common among neonates, even in stable disease. [ABSTRACT FROM AUTHOR]

Superhydrophobic surfaces with a slip effect have been proven to be effective to achieve surface drag reduction. In this paper, we fabricated superhydrophobic disks via laser ablation and chemical modification, and their drag-reduction performance is tested by a rheometer. However, the superhydrophobic disk achieves a limited drag-reduction effect (33.5% in maximum) with poor consistency (decay rapidly as rotating speed increases). To enhance the drag-reduction performance of the superhydrophobic surfaces, surfaces with tunable patterns consisting of superhydrophobic and hydrophobic surfaces are proposed. The difference in wettability and slip length between different regions is employed to control the flow direction. The effect of different patterns is investigated both experimentally and numerically, and the results indicate that the pattern distribution performs a great impact on the drag-reduction effect. The pattern consistent with the primary flow can not only enhance the effect (60.3% in maximum) but also the consistency (maintained at a higher rotating speed) of drag-reduction. On the contrary, the pattern perpendicular to the flow direction is harmful to drag reduction and can even increase the drag. [ABSTRACT FROM AUTHOR]

Spin caloritronic devices, as multifunctional devices, combining spintronics, and caloritronics, are essential for the sustainable development of humans. Here, a novel spin caloritronic device is presented using a diarylethene molecule photoswitch sandwiched among two semi-infinite zigzag graphene nanoribbons containing asymmetrical edge hydrogenation electrodes. We demonstrate that the temperature gradient between the right and the left electrodes can generate spin-up (SU) and spin-down (SD) currents moving in opposite orientations. Moreover, the mentioned currents possess approximately the same magnitudes, indicating a nearly nondissipative spin Seebeck effect. We also find that these currents are significantly dissimilar for the two photochromic isomers at different temperature gradients, demonstrating the excellent system's switching nature. The obtained results reveal that the light can control the thermal spin transport properties. [ABSTRACT FROM AUTHOR]

Emerging evidence suggests that neural activity contributes to tumor initiation and its acquisition of metastatic properties. More specifically, it has been reported that the sympathetic nervous system regulates tumor angiogenesis, tumor growth, and metastasis. The function of the sympathetic nervous system in primary tumors has been gradually elucidated. However, its functions in pre-metastatic environments and/or the preparation of metastatic environments far from the primary sites are still unknown. To investigate the role of the sympathetic nervous system in pre-metastatic environments, we performed chemical sympathectomy using 6-OHDA in mice and observed a decrease in lung metastasis by attenuating the recruitment of myeloid-derived suppressor cells. Furthermore, we note that neuro-immune cell interactions could be observed in tumor-bearing mouse lungs in conjunction with the decreased expression of Sema3A. These data indicate that the sympathetic nervous system contributes to the preparation of pre-metastatic microenvironments in the lungs, which are mediated by neuro-immune cell interactions. [ABSTRACT FROM AUTHOR]

Facile fabrication of rapid, firm, and reversible underwater adhesion used on different adherets is challenging but is of primary importance for many industrial and biomedical applications. Herein, tough, stretchy, moldable, and semitransparent gels are developed for self‐contained underwater adhesives. The selected structural components, well‐defined double‐network (DN) structures, and one‐pot synthesis realize synergistic adhesion and cohesion engineering, which deliver instant, solid, reversible, and long‐term adhesives with a high underwater adhesion strength of over 0.84 MPa. The underwater adhesion strength is among the best‐performing tape‐type underwater adhesives. In order to develop new energy‐related applications for underwater adhesion, the first example of combining underwater adhesion with solar power applications is demonstrated. Taking the benefits of the direct‐contact design at the air/water interface, the click‐gel‐mounted floating photovoltaic (FPV) system significantly increases the power conversion efficiency by 20% due to the enhanced active cooling effects, surpassing several conventional photovoltaic technologies on both land and water. The click‐gel also rapidly responds to several oscillatory motions on the FPV platform. This study shines a light on the facile fabrication of DN click‐gels for underwater adhesives and provides their future perspectives in energy‐wise, low‐maintenance, and stimuli‐responsive applications. [ABSTRACT FROM AUTHOR]

Metal-vapor deposition on polymer surfaces has been used in a variety of fields such electronics, food packing, and decorations. Polydimethylsiloxane (PDMS) is one of the widely used polymers. We studied a metal-deposition modulation phenomenon on a thermocurable PDMS. The metal atoms were easy to desorb from the uncured PDMS surface than from the cured surface. Furthermore, some metal atoms on the uncured surface were absorbed into the film and generated intrinsic color, which origins was suggested due to the size of metal nanoparticles. It was revealed that the differences in metal-deposition properties depended on the chain mobility of PDMS; uncured PDMS chains were in a high mobility state, while the cured PDMS surface had low mobility because of cross-linked chains. On the surface with high mobility molecules, metal atoms were easy to desorb and hard to nucleate due to the low density of metal atoms. Potential applications of metal-deposition modulation on thermocurable PDMS surfaces were proposed: three-dimensional metal-vapor integration, a mirror with no electronic conductance, and various colored Au patterns prepared with maskless vacuum deposition. These processes are simple one and any substrates including solid, flexible, flat, or curved can be used, and therefore, would be applied to a variety of fields. [ABSTRACT FROM AUTHOR]

This paper describes the challenges in the design of board-level Ku-band power amplifier (PA) using the hybrid-MIC technology. The selection of laminates, connectors, cables and RF components, such as DC feed and DC block, is examined from the perspective of Ku-band PA designers. Other key challenges, such as die mounting and wire bonding, are also discussed. Die mounting and wire bonding are critical phenomena and they have a great impact on the working of PA at high frequencies. After several trials, successful die mounting has been achieved and a methodology for reliable die mounting and wire bonding has been proposed. With the help of investigation done for the design of PA at the high operating frequency, a first board-level power amplifier at 17 GHz has been designed using a 250 nm bare die device with a 400 MHz frequency band. [ABSTRACT FROM AUTHOR]

Objective: To explore the effect of anti‐nuclear antibodies (ANAs) on the outcome of in vitro fertilization‐embryo transplantation (IVF‐ET) and to study the effect of ANAs in follicular fluid (FF) on embryonic development. Methods: The expression of ANAs in FF of patients treated with IVF‐ET and healthy group. The patients were divided into ANAs‐positive group and ANA‐negative group. The age, duration of infertility, body mass index (BMI), basic follicle stimulating hormone (bFSH), anti‐Mullerian hormone (AMH), number of retrieved oocytes, portion of metaphase II oocytes (MII), number of embryos in the cleavage stage, bipronuclear (2PN), number of embryos, number of high‐quality embryos and the outcome of IVF‐ET were compared between the two groups. In vitro, HTR8/SVneo trophoblast cells were cultivated and divided into ANAs‐negative group (control group) and ANAs‐positive group (ANAs‐positive FF was added to cytotrophoblasts). The ANAs titer in the serum and FF of patients who treated with IVF‐ET was detected using ELSIA method. CCK‐8 assay and flow cytometry (at 24 h and at 48 h) were used to detect the cell proliferation and apoptosis frequency of the two groups, respectively. Results: Among those who underwent IVF‐ET treatment, the number of retrieved oocytes, the number of fertilization and the portion of MII oocytes in the FF‐positive group were significantly lower than those in the FF‐negative group. Furthermore, the implantation rate and the clinical pregnancy rate were decreased, and early miscarriage rate was increased in the FF‐positive patients than those in the FF‐negative patients. In vitro, the cytotrophoblasts proliferation activity in the ANAs group was significantly lower than that in the control group. Moreover, the cytotrophoblasts apoptosis rate in the ANAs group was significantly higher than that in the control group. Conclusions: Our data suggested that ANAs in FF might become an obstacle to embryonic development through promoting trophoblast apoptosis and inhibiting trophoblast proliferation. ANAs in FF might be an unfavorable factor for the outcome of those who undergo IVF‐ET treatment. [ABSTRACT FROM AUTHOR]

A hydrogel is a polymer material with a porous network structure, which allows the hydrogel to swell rapidly underwater without dissolving. This unique property of hydrogels lays the foundation for their application in underwater adhesion. However, due to the existence of the hydration layer, the interaction between the hydrogel and the adherend surface is seriously hindered, and the underwater adhesion ability of the hydrogel is severely weakened. In the past few decades, various hydrogels for underwater adhesion have been developed, among which the underwater adhesion mechanisms of natural organisms have provided a steady stream of inspiration for researchers to design underwater adhesion hydrogels. In this review, we first summarize the adhesion mechanism and design strategies of underwater adhesion hydrogels, and then introduce the currently common experimental methods to test the adhesion strength and adhesion toughness of underwater adhesion hydrogels. According to the development trend in recent years, we summarize the common application fields of underwater adhesion hydrogels. Finally, we present our views on the challenges of hydrogels for underwater adhesion, and provide an outlook on future research directions. This review provides a comprehensive overview of underwater adhesion hydrogels, which will provide rational guidelines for the design and fabrication of underwater adhesion hydrogels. [ABSTRACT FROM AUTHOR]

Nonalcoholic steatohepatitis (NASH) is a severe form of liver injury that can be caused by a variety of stimuli and has a significant mortality rate. A common technique to induce in vitro steatosis involves culturing primary human hepatocytes (PHH) in fatty acid-enriched media. This study compared the lipidome of PHH cultured in fatty acid-enriched media to hepatocytes from patients with NASH and healthy controls. Hepatocytes from NASH patients displayed increased total cellular abundance of glycerolipids and phospholipids compared to healthy control hepatocytes. PHH cultured in fatty acidenriched media demonstrated increased glycerolipids. However, these culture conditions did not induce elevated phospholipid levels. Thus, culturing PHH in fatty acid-enriched media has limited capacity to emulate the environment of hepatocytes in NASH patients. [ABSTRACT FROM AUTHOR]

The use of optical coherence tomography (OCT) technology in anterior segment diseases allows for precise assessment of the changes following anterior segment surgery. Advances in microscope-integrated OCT systems have allowed the utilization of intraoperative OCT (iOCT) in anterior segment surgeries, i.e., cornea, cataract, and refractive surgery. iOCT has enabled real-time precise visualization of anterior segment tissues as well as interactions between surgical instruments and ocular tissue; thus, the device can facilitate surgical procedures and provide valuable information for decision-making during anterior segment surgeries. In this review, the authors will introduce studies regarding the development of iOCT technology and its application in various anterior segment surgeries. Multiple studies have shown the efficacy of the iOCT for intraoperative assistance and guidance, suggesting the potential of the device for optimizing the surgical outcomes after cornea, cataract, and refractive surgery. [ABSTRACT FROM AUTHOR]

Intraoperative optical coherence tomography (iOCT) is a noninvasive imaging technique that gives real-time dynamic feedback on surgical procedures. iOCT was first employed in vitreoretinal surgery, but successively served as a guidance in several anterior segment surgical approaches: keratoplasty, implantable Collamer lens (ICL) implantation, and cataract surgery. Among all of those approaches, the unbeatable features of iOCT are fully exploited in anterior and posterior lamellar keratoplasty, and the purpose of this review is to focus on the advantages and shortfalls of iOCT in these techniques, in order to assess whether this technology could be a real step forward. In deep anterior lamellar keratoplasty (DALK), iOCT is useful to evaluate the needle depth into the corneal stroma, the big bubble dissection plane, and residual stromal bed, thus aiding the standardization of the technique and the reduction of failures. In Descemet stripping automated endothelial keratoplasty (DSAEK), iOCT allowed for clear visibility of fluid at the graft/host interface, allowing for immediate rescue maneuvers and granting the best graft apposition. In Descemet membrane endothelial keratoplasty (DMEK), iOCT can track the lenticule unfolding in real time and assess graft orientation even in severe hazy corneas, thus optimizing surgical times, as well as avoiding the use of potentially hazardous exterior markers (such as the "S" stamp) and preventing unnecessary manipulation of the graft. Overall, the role of iOCT appeared crucial in several complicated cases, overcoming the difficulties of poor visualization in a fast, non-invasive way, thus raising this approach as possible gold standard for challenging conditions. Further improvements in the technology may enable autonomous centering and tracking, overcoming the current constraint of instrument-induced shadowing. [ABSTRACT FROM AUTHOR]

Background: Implantable Collamer lens (ICL) vaulting is one of the most important parameters for the safety, aqueous humor circulation, and lens transparency after ICL implantation. This study aimed to investigate the factors associated with the actual vaulting after refractive EVO-ICL surgery. Methods: This retrospective study included patients who underwent EVO-ICL surgery at a tertiary eye hospital between October and December 2019. A RESCAN 700 was used for the intraoperative and CIRRUS HD-OCT was used for postoperative observation of vaulting. Subjective and objective refractions, anterior ocular segment, corneal morphology, intraocular pressure (IOP), anterior chamber volume (ACV), crystalline lens rise (CLR), white-to-white distance (WTW), anterior chamber depth (ACD), axial length, corneal endothelial cell density (ECD), and fundoscopy were examined. A multivariable analysis was performed to determine the factors independently associated with 1-month postoperative vaulting. Results: Fifty-one patients (102 eyes) were included. Compared with the eyes with normal vaulting, those with high vaulting had higher preoperative diopter values (P = 0.039), lower preoperative corrected visual acuity (P = 0.006), lower preoperative IOP (P = 0.029), higher preoperative ACD (P = 0.004), lower preoperative CLR (P = 0.046), higher ICL spherical equivalent (P = 0.030), higher intraoperative vaulting (P < 0.001), and lower IOP at 1 month (P = 0.045). The multivariable analysis showed that the only factor independently associated with high vaulting at 1 month after surgery was the intraoperative vaulting value (odds ratio = 1.005, 95% confidence interval: 1.002–1.007, P < 0.001). The intraoperative and 1-month postoperative vaulting values were positively correlated (R2 = 0.562). Conclusions: The RESCAN700 system can be used to perform intraoperative optical coherence tomography to predict the vaulting value of ICL at 1 month. [ABSTRACT FROM AUTHOR]

Inhibiting AKTivity: The triggering receptor expressed on myeloid cells 2 (TREM2) has been implicated in the pathophysiology of Alzheimer's disease (AD), and the R47H variant of TREM2 gene is associated with increased risk of late onset AD. Here, Sayed et al. studied the mechanisms responsible for the detrimental effects of the variant. R47H-TREM2 results in increased expression of inflammatory molecules and enhanced AKT signaling in microglia from patients. The results were replicated in vivo using a knock-in mouse model. Moreover, the mutation worsened AD-like pathology and cognitive deficits in a model of tauopathy. Inhibiting AKT signaling had therapeutic effects in mice, suggesting that targeting AKT might be effective in patients with AD carrying the R47H mutation. The hemizygous R47H variant of triggering receptor expressed on myeloid cells 2 (TREM2), a microglia-specific gene in the brain, increases risk for late-onset Alzheimer's disease (AD). Using transcriptomic analysis of single nuclei from brain tissues of patients with AD carrying the R47H mutation or the common variant (CV)–TREM2, we found that R47H-associated microglial subpopulations had enhanced inflammatory signatures reminiscent of previously identified disease-associated microglia (DAM) and hyperactivation of AKT, one of the signaling pathways downstream of TREM2. We established a tauopathy mouse model with heterozygous knock-in of the human TREM2 with the R47H mutation or CV and found that R47H induced and exacerbated TAU-mediated spatial memory deficits in female mice. Single-cell transcriptomic analysis of microglia from these mice also revealed transcriptomic changes induced by R47H that had substantial overlaps with R47H microglia in human AD brains, including robust increases in proinflammatory cytokines, activation of AKT signaling, and elevation of a subset of DAM signatures. Pharmacological AKT inhibition with MK-2206 largely reversed the enhanced inflammatory signatures in primary R47H microglia treated with TAU fibrils. In R47H heterozygous tauopathy mice, MK-2206 treatment abolished a tauopathy-dependent microglial subcluster and rescued tauopathy-induced synapse loss. By uncovering disease-enhancing mechanisms of the R47H mutation conserved in human and mouse, our study supports inhibitors of AKT signaling as a microglial modulating strategy to treat AD. [ABSTRACT FROM AUTHOR]

An optical resolution of 3‐chloromandelic acid (3‐ClMA) using threo‐(1S,2S)‐2‐amino‐l‐p‐nitrophenyl‐1,3‐propanediol ([S,S]‐SA) as a resolving agent was presented. The effects of the type of solvents, the amount of solvent, molar ratio of the resolving agent to racemate and filtration temperature on resolution were investigated. Under the optimal resolution conditions, the content of less soluble salt reached 98%, and the resolution efficiency was as high as 94%. The weak intermolecular interactions (such as hydrogen bond, halogen bond, CH/π and van der Waals interactions) and molecular packing mode in crystal structure of the less soluble salt (R)‐3‐ClMA(S,S)‐SA were investigated. A wall‐like 2‐D hydrogen‐bonding network and hydrophobic structure between hydrogen‐bonding walls were revealed. (S,S)‐SA was also used to resolve 2‐ClMA and 4‐ClMA respectively and the corresponding less soluble salts (R)‐2‐ClMA·(R,R)‐SA and (R)‐4‐ClMA·(R,R)‐SA were obtained using threo‐(1R,2R)‐2‐amino‐l‐p‐nitrophenyl‐1,3‐propanediol ((R,R)‐SA) as a resolving agent. In addition, two other resolving agents, (R)‐ɑ‐phenethylamine ((R)‐PEA) and (R)‐N‐benzyl phenethylamine ((R)‐BPA) reported in the literature for the resolution of 3‐ClMA were examined along with the newly proposed resolving agent, (S,S)‐SA. The crystal structures of the resulting less soluble salts (R)‐3‐ClMA·(S,S)‐SA, (R)‐3‐ClMA·(R)‐PEA and (R)‐3‐ClMA·(R)‐BPA were compared and examined. [ABSTRACT FROM AUTHOR]

Homocoupling reactions promoted by photocatalysts are not very abundant in the literature. However, the products generated from such processes are very interesting. In this review, we highlight the most relevant reports concerning photocatalyzed dimerizations covering the literature until the middle of 2020. Reactions will be classified according to the type of starting material employed, with an emphasis being placed on the corresponding mechanism. 1 Introduction 2 Arenes and Heteroarenes 3 Alkenes 4 Alkanes 5 Alkynes 6 Aldehydes, Ketones, Alcohols, Amines and Imines 7 Carboxylic Acids 8 Nitro Compounds 9 Conclusions [ABSTRACT FROM AUTHOR]

Thrombocytes circulate in the blood of nonmammalian vertebrates and are involved in hemostasis; however, many detailed characteristics of thrombocytes remain unclear. Recently, we established an amphibian thrombocyte cell line. Here, we report the finding that thrombocytes produce integrin alpha IIb (CD41)‐positive extracellular vesicles (EVs), which include microRNAs (miRs). Flow cytometric analysis showed the expression of CD41+ and phosphatidylserine on the surface of EVs. Nanotracking analysis showed that these CD41+ EVs were approximately 100 nm in diameter. As CD41+ EVs were also observed from African clawed frogs, the production of CD41+ EVs might be common to amphibians. Microarray analysis showed that the CD41+ EVs contain many kinds of miRs. These CD41+ EVs were phagocytosed by endothelial cells and macrophages. qPCR analysis showed that many angiogenesis‐related genes were up‐regulated in CD41+ EV‐treated endothelial cells. Over‐expression of some miRs in the CD41+ EVs increased the proliferation of endothelial cells. These results indicated that thrombocytes produced CD41+ EVs, including miRs, that were received by endothelial cells to induce the expression of angiogenesis‐related genes. These results indicated that the CD41+ EVs produced from thrombocytes act as signaling molecules to repair damaged blood vessels. [ABSTRACT FROM AUTHOR]